Cardiovascular and lumenal stents are highly effective in the treatment of heart disease and other vascular conditions by the dilation and retention of constricted vessels or bodily conduits. However, their insertion may induce undesirable bodily reactions such as inflammation, infections, thrombosis or blood clots, restenosis, and proliferation of cell growth that occludes the passageway and may incur the need for additional surgery. Pharmaceutical drugs and compounds may assist in preventing these conditions, although they may be required in large oral or intravenous doses with stringent intake or injection timetables to increase their efficacy.
Pharmaceutical compounds may be coated directly on the stent to provide a preferable point-of-use drug delivery system, but these coatings must be bioengineered to control the release of sometimes highly potent and potentially toxic drugs. Timed-release attributes of a coating must be incorporated to avoid clinically unacceptable premature releases of toxic levels of potent drugs. Biocompatible, biodegradable polymers for various biomedical applications such as those used in sutures and tissue engineering have been described in “Functionalized Polyester Graft Copolymers,” Hrkach, et al., U.S. Pat. No. 5,654,381, issued Aug. 5, 1997. Drug-polymers based on polylactide and drug mixtures in particle or pellet form to provide timed-release delivery are described in “Polylactide-Drug Mixtures,” Boswell, et al., U.S. Pat. No. 3,773,919, issued Nov. 20, 1973, or in a spray form as described in “Polylactide-Drug Mixtures for Topical Application,” Scribner, et al., U.S. Pat. No. 3,755,558, issued Aug. 28, 1973.
These developments in pharmaceutical coatings, however, have limited control over the delivery of the drug and versatility in the types of drugs to be delivered and their pharmacodynamics. The delivery of the drug may be too fast, ineffective and possibly toxic, or too slow and ineffective. The drug coating may not stick or adhere. The drug polymer coatings should coat the stent framework without cracking, peeling or delaminating, particularly when the stent is expanded during installation. The coating should not fall off, crack, fracture, crystallize or melt during processing, sterilizing, or installing. In some cases, a rapid delivery of a drug may be needed immediately following surgery, followed by a steady delivery of the drug at a lesser rate over an extended period of time. Because there is need for the in vivo delivery of more than one drug, delivery of one or multiple drug types from a deployed, coated stent with variable elution rates is desirable. One drug type in a polymer coating may elute faster than another drug type in the same polymer, thus methods of modulating a drug without impacting its bioactive moiety are desirable.
In spite of the broad coverage of the prior art on the use endovascular stents for the prevention of restenosis entailing many types of stent polymeric barrier coatings and bioactive agents for inhibiting restenosis, integrating the role of both components into a physico-pharmacologically unique entity to maximize their efficacy as a physical barrier and pharmacologically active agent was left unaddressed. This and the availability of new forms of bioactive agents with more than one pharmacological effect provided an incentive to explore the concept of multifaceted coating composition subject of this invention.